By Richard Karel

The sun was back--for about an hour a day--in Tromso, Norway, after 39 days of total darkness, and it was cause for much rejoicing.

In mid-January, Tromso, which is north of the Arctic Circle, played host to "SAD '97: Consensus, Controversies, and Clinical Management." At about the same time, a new study in hamsters (published as scientific correspondence in the January 9 issue of Nature) strengthened the case for the link between light, depression, and serotonin. As the veil of winter darkness began to lift from Tromso to Tucson, scientists struggled to illuminate the mystery of the mammalian brain's remarkable capacity to transmute light into the biochemical components of mood and movement.

Light therapy has become one of the popular methods of treating winter depression, or SAD (seasonal affective disorder). In theory, prolonging short winter days with artificial bright light alters circadian rhythms that in some people trigger winter depression. But the observation that artificial bright light can be effective in treating SAD even when presented in midday is inconsistent with the hypothesis that light therapy works by mediating circadian phase changes linked to short winter days.

With this inconsistency in mind, Fred Turek, Ph.D., director of the Center for Circadian Biology and Medicine at Northwestern University in Evanston, Ill., set out with his colleagues to investigate what happens in the brains of golden hamsters who have their circadian rhythms altered by the serotonin agonist 8-OH-DPAT (8-hydroxy-dipropylaminotetralin) with and without exposure to two hours of bright light during the subjective day.

They administered the substance to two groups of hamsters, but exposed one group to two hours of full-spectrum light during the day. Although light alone had no effect on circadian phase in the control group, it virtually negated the phase-resetting properties of 8-OH-DPAT.

"The essence of our study is that at a time of day when we know that light has no effect [on the circadian clock], serotonin will shift the clock," Turek told Psychiatric News. "If we give light and serotonin [an agonist] at the same time, [light] blocks the effect of serotonin. If light can alter the way that neural tissue, the brain of a hamster, can respond to exogenous serotonergic stimulation, it raises the hypothesis that light may alter the way the brain is responding to serotonin in the brain."

It is clear that light impulses have a direct impact on the brain through the optic nerves into the suprachiasmatic nucleus of the hypothalamus, said Turek. "That light information is somehow able to synchronize the endogenous neuroclock" from within the suprachiasmatic nucleus.

Light is effective in treating SAD, observed Turek, yet understanding of its actions remains rudimentary. Similarly, there is but imprecise understanding of how serotonin-enhancing drugs like Prozac (fluoxetine) and Zoloft (sertraline) exert their effects, Turek observed. While they inhibit reuptake of serotonin at the receptor, "we don't know how that translates into alleviating depression. We need to begin to address physiological mechanisms here." So it was logical to ask whether light would affect serotonergic function, he added.

Norman Rosenthal, M.D., chief of the Section on Environmental Psychiatry at the National Institute of Mental Health (NIMH), spoke with Psychiatric News from Tromso, where he was chairing the SAD conference.

"I think what the Turek article does is indicate interaction between light and a serotonergic drug in an animal model. It's not the first time in animals that light and serotonin have somehow been connected with each other." Earlier work has shown that light exposure alters the firing rate of serotonergic neurons in rats. Another study found that the amount of light influences the concentration of serotonin in the rat brain.

Further, the evidence is "very powerful that light modifies the response of serotonin in humans," he added. For example, Rosenthal and colleagues at NIMH found that untreated SAD sufferers infused with the serotonin agonist m-CPP become animated and euphoric. But there was no abnormal activation and euphoria when they were treated with artificial light or given m-CPP in the summer. "That is analogous in the human domain to what Turek has found in the animal domain," noted Rosenthal.

"Two separate studies have shown if you [artificially] deplete light-treated SAD patients of serotonin [after they are better], they will relapse, indicating once again that light treatment for SAD is probably working through the serotonergic system."

What is the next step? "If light is an effective serotonergic intervention, why should it not be effective for other syndromes where serotonergic abnormality has been hypothesized?"

One small study found light to be effective in the treatment of bulimia, a disorder highly sensitive to seasonal fluctuation, said Rosenthal. Moreover, in an Austrian study of patients with nonseasonal depression who were unresponsive to fluoxetine alone, three weeks of morning light exposure combined with fluoxetine achieved a positive response.

For psychiatrists, "the bottom line is that there are several clinical studies suggesting that serotonergic function in the brain is abnormal in seasonal affective disorder," Rosenthal stressed. None of the studies suggest a circadian mechanism, which means that the Turek study "corroborates what we and others have shown through clinical research into interactions between the serotonin systems and light." (Psychiatric News, February 7, 1997)